Large randomized study of thymosin α 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma

Michele Maio, Andrzej Mackiewicz, Alessandro Testori, Uwe Trefzer, Virginia Ferraresi, Jacek Jassem, Claus Garbe, Thierry Lesimple, Bernard Guillot, Pere Gascon, K. Gilde, Roberto Camerini, Francesco Cognetti

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Abstract

Purpose: Thymosin α 1 (Tα1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Tα1 with dacarbazine (DTIC) and interferon alfa (IFN-α) in patients with metastatic melanoma. Patients and Methods: Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-α+Tα1 (1.6 mg); DTIC+IFN-α+Tα1 (3.2 mg); DTIC+IFN-α+Tα1 (6.4 mg); DTIC+Tα1 (3.2 mg); DTIC+IFN-α (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months. Results: Ten and 12 tumor responses were observed in the DTIC+IFN-α+Tα1 (3.2 mg) and DTIC+Tα1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P0 ≤ .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Tα1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Tα1 versus 6.6 months in the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Tα1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of Tα1 to DTIC and IFN-α did not lead to any additional toxicity. Conclusion: These results suggest Tα1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.

Original languageEnglish
Pages (from-to)1780-1787
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number10
DOIs
Publication statusPublished - Apr 1 2010

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Thymosin
Dacarbazine
Interferons
Melanoma
Interferon-alpha
Control Groups
thymalfasin
Disease-Free Survival
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Large randomized study of thymosin α 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. / Maio, Michele; Mackiewicz, Andrzej; Testori, Alessandro; Trefzer, Uwe; Ferraresi, Virginia; Jassem, Jacek; Garbe, Claus; Lesimple, Thierry; Guillot, Bernard; Gascon, Pere; Gilde, K.; Camerini, Roberto; Cognetti, Francesco.

In: Journal of Clinical Oncology, Vol. 28, No. 10, 01.04.2010, p. 1780-1787.

Research output: Contribution to journalArticle

Maio, M, Mackiewicz, A, Testori, A, Trefzer, U, Ferraresi, V, Jassem, J, Garbe, C, Lesimple, T, Guillot, B, Gascon, P, Gilde, K, Camerini, R & Cognetti, F 2010, 'Large randomized study of thymosin α 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma', Journal of Clinical Oncology, vol. 28, no. 10, pp. 1780-1787. https://doi.org/10.1200/JCO.2009.25.5208
Maio, Michele ; Mackiewicz, Andrzej ; Testori, Alessandro ; Trefzer, Uwe ; Ferraresi, Virginia ; Jassem, Jacek ; Garbe, Claus ; Lesimple, Thierry ; Guillot, Bernard ; Gascon, Pere ; Gilde, K. ; Camerini, Roberto ; Cognetti, Francesco. / Large randomized study of thymosin α 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 10. pp. 1780-1787.
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abstract = "Purpose: Thymosin α 1 (Tα1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Tα1 with dacarbazine (DTIC) and interferon alfa (IFN-α) in patients with metastatic melanoma. Patients and Methods: Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-α+Tα1 (1.6 mg); DTIC+IFN-α+Tα1 (3.2 mg); DTIC+IFN-α+Tα1 (6.4 mg); DTIC+Tα1 (3.2 mg); DTIC+IFN-α (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months. Results: Ten and 12 tumor responses were observed in the DTIC+IFN-α+Tα1 (3.2 mg) and DTIC+Tα1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P0 ≤ .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Tα1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Tα1 versus 6.6 months in the control group (hazard ratio = 0.80; 95{\%} CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Tα1 versus the control group (hazard ratio = 0.80; 95{\%} CI, 0.63 to 1.01; P = .06). Addition of Tα1 to DTIC and IFN-α did not lead to any additional toxicity. Conclusion: These results suggest Tα1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.",
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AU - Mackiewicz, Andrzej

AU - Testori, Alessandro

AU - Trefzer, Uwe

AU - Ferraresi, Virginia

AU - Jassem, Jacek

AU - Garbe, Claus

AU - Lesimple, Thierry

AU - Guillot, Bernard

AU - Gascon, Pere

AU - Gilde, K.

AU - Camerini, Roberto

AU - Cognetti, Francesco

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N2 - Purpose: Thymosin α 1 (Tα1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Tα1 with dacarbazine (DTIC) and interferon alfa (IFN-α) in patients with metastatic melanoma. Patients and Methods: Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-α+Tα1 (1.6 mg); DTIC+IFN-α+Tα1 (3.2 mg); DTIC+IFN-α+Tα1 (6.4 mg); DTIC+Tα1 (3.2 mg); DTIC+IFN-α (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months. Results: Ten and 12 tumor responses were observed in the DTIC+IFN-α+Tα1 (3.2 mg) and DTIC+Tα1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P0 ≤ .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Tα1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Tα1 versus 6.6 months in the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Tα1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of Tα1 to DTIC and IFN-α did not lead to any additional toxicity. Conclusion: These results suggest Tα1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.

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